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    F8 coagulation factor VIII [ Homo sapiens (human) ]

    Gene ID: 2157, updated on 10-Dec-2017
    Official Symbol
    F8provided by HGNC
    Official Full Name
    coagulation factor VIIIprovided by HGNC
    Primary source
    HGNC:HGNC:3546
    See related
    Ensembl:ENSG00000185010 MIM:300841; Vega:OTTHUMG00000022688
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    AHF; F8B; F8C; HEMA; FVIII; DXS1253E
    Summary
    This gene encodes coagulation factor VIII, which participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in fat (RPKM 7.9), lung (RPKM 6.4) and 23 other tissues See more
    Orthologs
    Location:
    Xq28
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) X NC_000023.11 (154835788..155022723, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (154064063..154255351, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 37 Neighboring gene small integral membrane protein 9 Neighboring gene microRNA 1184-1 Neighboring gene H2A histone family member B1 Neighboring gene coagulation factor VIII associated 1 Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 31 Neighboring gene zinc finger protein 622 pseudogene Neighboring gene FUN14 domain containing 2 Neighboring gene mature T cell proliferation 1 Neighboring gene C-X9-C motif containing 4

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Hereditary factor VIII deficiency disease
    MedGen: C0019069 OMIM: 306700 GeneReviews: Hemophilia A
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2012-04-05)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated (2012-04-05)

    ClinGen Genome Curation Page

    NHGRI GWAS Catalog

    Description
    Genetically distinct subsets within ANCA-associated vasculitis.
    NHGRI GWA Catalog
    Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120-treated vaginal epithelial cells show upregulation of coagulation factor VIII (F8) expression as compared to untreated control PubMed

    Go to the HIV-1, Human Interaction Database

    • Asparagine N-linked glycosylation, organism-specific biosystem (from REACTOME)
      Asparagine N-linked glycosylation, organism-specific biosystemN-linked glycosylation is the most important form of post-translational modification for proteins synthesized and folded in the Endoplasmic Reticulum (Stanley et al. 2009). An early study in 1999 rev...
    • Blood Clotting Cascade, organism-specific biosystem (from WikiPathways)
      Blood Clotting Cascade, organism-specific biosystemCoagulation is a complex process by which blood forms clots. It is an important part of hemostasis (the cessation of blood loss from a damaged vessel), wherein a damaged blood vessel wall is covered ...
    • COPII (Coat Protein 2) Mediated Vesicle Transport, organism-specific biosystem (from REACTOME)
      COPII (Coat Protein 2) Mediated Vesicle Transport, organism-specific biosystemCOPII components (known as Sec13p, Sec23p, Sec24p, Sec31p, and Sar1p in yeast) traffic cargo from the endoplasmic reticulum to the ER-Golgi intermediate compartment (ERGIC). COPII-coated vesicles wer...
    • Cargo concentration in the ER, organism-specific biosystem (from REACTOME)
      Cargo concentration in the ER, organism-specific biosystemComputational analysis suggests that ~25% of the proteome may be exported from the ER in human cells (Kanapin et al, 2003). These cargo need to be recognized and concentrated into COPII vesicles, wh...
    • Common Pathway of Fibrin Clot Formation, organism-specific biosystem (from REACTOME)
      Common Pathway of Fibrin Clot Formation, organism-specific biosystemThe common pathway consists of the cascade of activation events leading from the formation of activated factor X to the formation of active thrombin, the cleavage of fibrinogen by thrombin, and the f...
    • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
      Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
    • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
      Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
    • Complement and coagulation cascades, conserved biosystem (from KEGG)
      Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
    • ER to Golgi Anterograde Transport, organism-specific biosystem (from REACTOME)
      ER to Golgi Anterograde Transport, organism-specific biosystemSecretory cargo destined to be secreted or to arrive at the plasma membrane (PM) leaves the ER via distinct exit sites. This cargo is destined for the Golgi apparatus for further processing.
    • Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystem (from REACTOME)
      Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystemThe formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to ...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Intrinsic Pathway of Fibrin Clot Formation, organism-specific biosystem (from REACTOME)
      Intrinsic Pathway of Fibrin Clot Formation, organism-specific biosystemThe intrinsic pathway of blood clotting connects interactions among kininogen (high molecular weight kininogen, HK), prekallikrein (PK), and factor XII to the activation of clotting factor X by a ser...
    • Membrane Trafficking, organism-specific biosystem (from REACTOME)
      Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
      Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
    • Platelet degranulation, organism-specific biosystem (from REACTOME)
      Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
    • Post-translational protein modification, organism-specific biosystem (from REACTOME)
      Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
    • Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
      Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
    • Transport to the Golgi and subsequent modification, organism-specific biosystem (from REACTOME)
      Transport to the Golgi and subsequent modification, organism-specific biosystemAt least two mechanisms of transport of proteins from the ER to the Golgi have been described. One is a general flow requiring no export signals (Wieland et al, 1987; Martinez-Menarguez et al, 1999)....
    • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
      Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    copper ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    oxidoreductase activity IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    COPII vesicle coating TAS
    Traceable Author Statement
    more info
     
    ER to Golgi vesicle-mediated transport TAS
    Traceable Author Statement
    more info
     
    acute-phase response IEA
    Inferred from Electronic Annotation
    more info
     
    blood coagulation TAS
    Traceable Author Statement
    more info
     
    blood coagulation, intrinsic pathway TAS
    Traceable Author Statement
    more info
     
    oxidation-reduction process IEA
    Inferred from Electronic Annotation
    more info
     
    platelet activation IEA
    Inferred from Electronic Annotation
    more info
     
    platelet degranulation TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    COPII-coated ER to Golgi transport vesicle TAS
    Traceable Author Statement
    more info
     
    Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
     
    endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
     
    endoplasmic reticulum-Golgi intermediate compartment membrane TAS
    Traceable Author Statement
    more info
     
    extracellular region NAS
    Non-traceable Author Statement
    more info
    PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space IEA
    Inferred from Electronic Annotation
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    platelet alpha granule lumen TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    coagulation factor VIII
    Names
    antihemophilic factor
    coagulation factor VIII A1 domain
    coagulation factor VIII C2 domain
    coagulation factor VIII, procoagulant component
    coagulation factor VIIIc
    factor VIII F8B

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011403.1 RefSeqGene

      Range
      5001..191936
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000132.3NP_000123.1  coagulation factor VIII isoform a preproprotein

      See identical proteins and their annotated locations for NP_000123.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) consists of 26 exons and encodes the full-length isoform (a).
      Source sequence(s)
      BC022513, M14113
      Consensus CDS
      CCDS35457.1
      UniProtKB/Swiss-Prot
      P00451
      Related
      ENSP00000353393.4, OTTHUMP00000024269, ENST00000360256.8, OTTHUMT00000058869
      Conserved Domains (8) summary
      smart00231
      Location:20392188
      FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain
      cd00057
      Location:21952344
      FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.
      cd04227
      Location:399575
      CuRO_3_FVIII_like; The third cupredoxin domain of coagulation factor VIII and similar proteins
      cd04228
      Location:17141880
      CuRO_5_FVIII_like; The fifth cupredoxin domain of coagulation factor VIII and similar proteins
      cd11015
      Location:211345
      CuRO_2_FVIII_like; The second cupredoxin domain of coagulation factor VIII and similar proteins
      cd11016
      Location:588730
      CuRO_4_FVIII_like; The fourth cupredoxin domain of coagulation factor VIII and similar proteins
      cd11018
      Location:18922035
      CuRO_6_FVIII_like; The sixth cupredoxin domain of coagulation factor VIII and similar proteins
      cd14452
      Location:22201
      CuRO_1_FVIII_like; The first cupredoxin domain of coagulation factor VIII and similar proteins
    2. NM_019863.2NP_063916.1  coagulation factor VIII isoform b

      See identical proteins and their annotated locations for NP_063916.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an unique 5' exon located within intron 22 of transcript variant 1. This exon codes for eight amino acids and is spliced to exons 23-26 maintaining the reading frame. The resulting isoform (b) is considerably shorter compared to isoform a, and includes the phospholipid binding domain.
      Source sequence(s)
      BC022513, BC064380, BI547023
      Consensus CDS
      CCDS44026.1
      UniProtKB/Swiss-Prot
      P00451
      Related
      ENSP00000327895.6, OTTHUMP00000196174, ENST00000330287.10, OTTHUMT00000083107
      Conserved Domains (2) summary
      cd00057
      Location:60209
      FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.
      cl25480
      Location:452
      FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p7 Primary Assembly

      Range
      154835788..155022723 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018934.2 Alternate CHM1_1.1

      Range
      153975773..154162623 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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